Nasal insulin delivery remains a possible alternative for patients with diabetes mellitus in attempting to control blood glucose levels. Nasal insulin administration requires the addition of a surfactant agent to improve systemic absorption of insulin, but this requirement has led to difficulty in identifying safe, effective surfactant agents that could be included in a nasal formulation. Pilot studies by the investigators have shown that some alkylglycosides were effective in promoting insulin absorption following nasal delivery. Alkylglycosides with longer alkyl side chains (i.e. 12-14 carbons in length) were the most effective in enhancing insulin absorption, whereas alkylglycosides with shorter side chains (i.e. 6- 8 carbons in length) were ineffective. In Phase I of this investigation, alkylglycosides with side chains containing 14- 16 carbons were synthesized and their efficacy in enhancing nasal insulin delivery was determined. Tetradecylmaltoside, an alkylglycoside with a 14 carbon side chain, was the most effective reagent at increasing nasal insulin delivery. Independently, this reagent caused little nasal toxicity when applied to rats once a day for 15 days. The extent of the nasal toxicity was dependent on the tetradecylmaltoside concentration used. Phase II studies are intended to; l) assess the stability of nasal insulin formulations containing tetradecylmaltoside; 2) compare the efficacy of nosedrops containing insulin and tetradecylmaltoside verses nasal mist or aerosol of the same formulation in primarily rats (but also rabbits and monkeys too); 3) compare the onset and duration of action of nasal insulin delivery when rapid-acting insulin or intermediate-acting insulin are substituted for regular insulin. (Preliminary data in Appendix l indicates that monomeric LysPro-insulin, regular or NPH-insulin with 0.125% dodecylmaltoside were as efficiently absorbed as each other, giving similar pharmacokinetic/pharmakodynamic profiles); 4) determine the formulation to bring to clinical trials. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE